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Chromosome breakage

About: Chromosome breakage is a research topic. Over the lifetime, 2994 publications have been published within this topic receiving 157662 citations.


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Journal ArticleDOI
Yosef Shiloh1
TL;DR: Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers.
Abstract: Maintenance of genome stability is essential for avoiding the passage to neoplasia. The DNA-damage response--a cornerstone of genome stability--occurs by a swift transduction of the DNA-damage signal to many cellular pathways. A prime example is the cellular response to DNA double-strand breaks, which activate the ATM protein kinase that, in turn, modulates numerous signalling pathways. ATM mutations lead to the cancer-predisposing genetic disorder ataxia-telangiectasia (A-T). Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers.

2,579 citations

Journal ArticleDOI
16 Nov 1984-Science
TL;DR: An attempt is made to outline several experiments conducted by the author that revealed how a genome may react to conditions for which it is unprepared, but to which it responds in a discernible, but initially unforeseen manner.
Abstract: An attempt is made to outline several experiments conducted by the author that revealed how a genome may react to conditions for which it is unprepared, but to which it responds in a discernible, but initially unforeseen manner. One of the experiments involves the effect of X-rays on chromosomes of maize. 35 references, 3 figures.

2,293 citations

Journal ArticleDOI
TL;DR: In its current basic form the CBMN assay can provide the following measures of genotoxicity and cytotoxicity: chromosome breakage, chromosome loss, chromosome rearrangement, cell division inhibition, necrosis and apoptosis.
Abstract: The study of DNA damage at the chromosome level is an essential part of genetic toxicology because chromosomal mutation is an important event in carcinogenesis. The micronucleus assays have emerged as one of the preferred methods for assessing chromosome damage because they enable both chromosome loss and chromosome breakage to be measured reliably. Because micronuclei can only be expressed in cells that complete nuclear division a special method was developed that identifies such cells by their binucleate appearance when blocked from performing cytokinesis by cytochalasin-B (Cyt-B), a microfilament-assembly inhibitor. The cytokinesis-block micronucleus (CBMN) assay allows better precision because the data obtained are not confounded by altered cell division kinetics caused by cytotoxicity of agents tested or sub-optimal cell culture conditions. The method is now applied to various cell types for population monitoring of genetic damage, screening of chemicals for genotoxic potential and for specific purposes such as the prediction of the radiosensitivity of tumours and the inter-individual variation in radiosensitivity. In its current basic form the CBMN assay can provide, using simple morphological criteria, the following measures of genotoxicity and cytotoxicity: chromosome breakage, chromosome loss, chromosome rearrangement (nucleoplasmic bridges), cell division inhibition, necrosis and apoptosis. The cytosine-arabinoside modification of the CBMN assay allows for measurement of excision repairable lesions. The use of molecular probes enables chromosome loss to be distinguished from chromosome breakage and importantly non-disjunction in non-micronucleated binucleated cells can be efficiently measured. The in vitro CBMN technique, therefore, provides multiple and complementary measures of genotoxicity and cytotoxicity which can be achieved with relative ease within one system. The basic principles and methods (including detailed scoring criteria for all the genotoxicity and cytotoxicity end-points) of the CBMN assay are described and areas for future development identified.

2,287 citations

Journal ArticleDOI
TL;DR: The cytokinesis-block micronucleus cytome assay is a comprehensive system for measuring DNA damage, cytostasis and cytotoxicity and is being applied successfully for biomonitoring of in vivo genotoxin exposure, in vitro genotoxicity testing and in diverse research fields such as nutrigenomics and pharmacogenomics as a predictor of normal tissue and tumor radiation sensitivity and cancer risk.
Abstract: The cytokinesis-block micronucleus cytome assay is a comprehensive system for measuring DNA damage, cytostasis and cytotoxicity. DNA damage events are scored specifically in once-divided binucleated (BN) cells and include (a) micronuclei (MNi), a biomarker of chromosome breakage and/or whole chromosome loss, (b) nucleoplasmic bridges (NPBs), a biomarker of DNA misrepair and/or telomere end-fusions, and (c) nuclear buds (NBUDs), a biomarker of elimination of amplified DNA and/or DNA repair complexes. Cytostatic effects are measured via the proportion of mono-, bi- and multinucleated cells and cytotoxicity via necrotic and/or apoptotic cell ratios. Further information regarding mechanisms leading to MNi, NPBs and NBUDs formation is obtained using centromere and/or telomere probes. The assay is being applied successfully for biomonitoring of in vivo genotoxin exposure, in vitro genotoxicity testing and in diverse research fields such as nutrigenomics and pharmacogenomics as well as a predictor of normal tissue and tumor radiation sensitivity and cancer risk. The procedure can take up to 5 days to complete.

1,698 citations

Journal ArticleDOI
08 Mar 1941-Genetics
TL;DR: This article constitutes part of McClintock's larger body of work on ring chromosomes in which she found that the chromatid breakage-fusion-bridge cycle occurred only in the germ cells and endosperm, while the chromosome BFB continued in the sporophyte, which meant that she could selectively produce persistent variegation in plant tissues.
Abstract: This article constitutes part of McClintock's larger body of work on ring chromosomes in which she found that the chromatid breakage-fusion-bridge (BFB) cycle occurred only in the germ cells and endosperm, while the chromosome BFB continued in the sporophyte, which meant that she could selectively produce persistent variegation in plant tissues.

1,520 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202124
202027
201929
201845
201732
201657